Academic Journal
Host immunosuppression and antifungal pressure cooperatively shape fungal adaptation and pulmonary microenvironment in cryptococcosis.
| Τίτλος: | Host immunosuppression and antifungal pressure cooperatively shape fungal adaptation and pulmonary microenvironment in cryptococcosis. |
|---|---|
| Συγγραφείς: | Alves V; Laboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., R de S Araujo G; Laboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Miranda B; Laboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Avellar-Moura I; Laboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Bastos de Andrade I; Laboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Corrêa-Junior D; Laboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Pereira L; Laboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Rodrigues Alves T; Laboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Carraro D; Laboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Luckshal M; Laboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Cruz F; Laboratório de Investigação Pulmonar, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., J Guimarães A; Laboratório de Bioquímica e Imunologia das Micoses, Departamento de Microbiologia e Parasitologia, Universidade Federal Fluminense, Niterói, Rio de Janeiro, Brazil; Rede Micologia - FAPERJ, Rio de Janeiro, Brazil., Maeda Takiya C; Laboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Frases S; Laboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; Rede Micologia - FAPERJ, Rio de Janeiro, Brazil. Electronic address: susanafrases@biof.ufrj.br. |
| Πηγή: | Microbial pathogenesis [Microb Pathog] 2026 Sep; Vol. 218, pp. 108688. Date of Electronic Publication: 2026 Jul 07. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Academic Press Country of Publication: England NLM ID: 8606191 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-1208 (Electronic) Linking ISSN: 08824010 NLM ISO Abbreviation: Microb Pathog Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: London ; Orlando : Academic Press, c1986- |
| Ιατρικοί όροι (MeSH): | Cryptococcosis*/drug therapy , Cryptococcosis*/immunology , Cryptococcosis*/microbiology , Cryptococcosis*/pathology , Cryptococcus neoformans*/drug effects , Cryptococcus neoformans*/immunology , Cryptococcus neoformans*/pathogenicity , Cryptococcus neoformans*/physiology , Antifungal Agents*/pharmacology , Antifungal Agents*/therapeutic use , Lung*/microbiology , Lung*/pathology , Lung*/immunology , Host-Pathogen Interactions*/immunology , Host-Pathogen Interactions*/drug effects , Immunosuppression Therapy*, Dexamethasone/pharmacology ; Fluconazole/pharmacology ; Fluconazole/therapeutic use ; Bronchoalveolar Lavage Fluid/microbiology ; Macrophages/immunology ; Animals ; Mice ; Disease Models, Animal ; Mice, Inbred C57BL |
| Περίληψη: | Cryptococcus neoformans remains a major opportunistic pathogen causing life-threatening pulmonary and systemic infections in immunocompromised individuals. Effective disease control is challenged by limited therapeutic options and by the pathogen's remarkable ability to adapt under immune and pharmacological pressures. Corticosteroids, while indispensable for managing inflammatory and autoimmune conditions, can disrupt immune homeostasis and worsen fungal infections. To investigate how corticosteroid-induced immunosuppression interacts with antifungal therapy, we employed a murine model of pulmonary cryptococcosis. Dexamethasone treatment promoted fungal proliferation, decreased CD45+ leukocyte infiltration, and induced excessive neutrophilic activity, evidenced by enhanced MPO+ staining. It also upregulated the expression of mannose receptor, indicating macrophage polarization toward an alternatively activated M2-like phenotype, and caused laminin degradation, culminating in severe pulmonary injury. In contrast, fluconazole reduced fungal burden, preserved lung architecture, and partially restored immune and extracellular matrix balance, even in combination with dexamethasone. Yeasts recovered from bronchoalveolar lavage fluid and lung tissue exhibited distinct adaptive profiles depending on treatment and anatomical origin, including alterations in capsule size, titan cell formation, chitin remodeling, lipid accumulation, and polysaccharide secretion. Dexamethasone-driven reductions in viscosity and loss tangent at intermediate frequencies mechanically relax the alveolar lumen, potentially enabling more efficient fungal displacement and dissemination. Collectively, these findings demonstrate how immunosuppressive and antifungal pressures jointly influence fungal adaptation, immune dynamics, and pulmonary biomechanics, providing integrated insights into host-pathogen-drug interactions that are relevant for optimizing cryptococcosis therapy. (Copyright © 2026 The Authors. Published by Elsevier Ltd.. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Susana Frases reports financial support was provided by Carlos Chagas Filho Foundation for Research Support of Rio de Janeiro State. Susana Frases reports financial support was provided by National Council for Scientific and Technological Development. Susana Frases reports financial support was provided by Coordination for the improvement of Higher Education Personnel. Susana Frases reports a relationship with Carlos Chagas Filho Foundation for Research Support of Rio de Janeiro State that includes: funding grants. Susana Frases reports a relationship with Coordination for the improvement of Higher Education Personnel that includes: funding grants. Susana Frases reports a relationship with National Council for Scientific and Technological Development that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Antifungal therapy; Cryptococcus neoformans; Immunosuppression; Pulmonary pathogenesis |
| Substance Nomenclature: | 0 (Antifungal Agents) 7S5I7G3JQL (Dexamethasone) 8VZV102JFY (Fluconazole) |
| Entry Date(s): | Date Created: 20260707 Date Completed: 20260718 Latest Revision: 20260718 |
| Update Code: | 20260719 |
| DOI: | 10.1016/j.micpath.2026.108688 |
| PMID: | 42413740 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1096-1208 |
|---|---|
| DOI: | 10.1016/j.micpath.2026.108688 |